Endstage renal failure (ESRD) is a major medical problem, contributing substantially to patient morbidity and mortality and constituting a major stress to the solvency of the national health care system. Recent experiments in animals have suggested that progression of renal insufficiency to ESRD may involve a common mechanism, glomerular hyperfiltration, irrespective of the initiating mechanism. Further, this work in experimental animals has suggested that progression of hyperfiltration injury may be slowed or halted by administration of a protein restricted diet. This grant application is in response to NIH RFA NIADDK 83-1 to collaborate in a multicenter clinical trial of the effectiveness of a low protein diet in reducing the rate of progression of early renal insufficiency to ESRD, and to test the safety and patient acceptance of this diet. We propose that patients with early renal insufficiency (serum creatinines between 2.0 and 6.0 mg/dl) and who are otherwise well and free from disease or medical therapy that would influence protein metabolism be admitted to the trial. Patients will undergo extensive dietary education and repeated renal function testing during an initial two month period. Patients with rapidly progressing renal insufficiency and those judged unlikely to comply with the prescribed diet will be eliminated prior to randomization. Patients will then be randomized either to a test diet containing 0.6 g/kg of protein (75% of high biological value) or to a control diet unrestricted in protein. Patients will be followed for an additional four months to maximize compliance to the diet and to measure any changes in renal function resulting from the diet itself. At the end of this period baseline glomerular filtration rate (GFR) will be measured by a single dose radioisotopic method. Patients will then be followed for periods up to five years, with periodic determinations of GFR, of compliance to diet, and of protein nutritional status. Blood pressure and urinary protein excretion will be followed as additional indicators of progression of glomerular damage. Considerable attention will be paid to monitoring and encouraging patient compliance, which is likely to prove one of the limiting factors in this study. Outcome will be judged by comparison of the rate of change of GFR in the two groups, by the rate with which the patients have serious decline in renal function or progression to ESRD, by the results of the tests of nutritional safety of the diet, and by the degree of patient compliance that can be obtained.